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Title

A virus-encoded type I interferon decoy receptor enables evasion of host immunity through cell-surface binding

AuthorsHernáez, Bruno ; Alonso-Lobo, Juan M.; Montanuy, Inmaculada ; Fischer, Cornelius; Sauer, Sascha; Sigal, Luis; Sevilla, Noemí ; Alcamí, Antonio
Issue Date2018
PublisherNature Publishing Group
CitationNature Communications 9 (2018)
AbstractSoluble cytokine decoy receptors are potent immune modulatory reagents with therapeutic applications. Some virus-encoded secreted cytokine receptors interact with glycosaminoglycans expressed at the cell surface, but the biological significance of this activity in vivo is poorly understood. Here, we show the type I interferon binding protein (IFNα/βBP) encoded by vaccinia and ectromelia viruses requires of this cell binding activity to confer full virulence to these viruses and to retain immunomodulatory activity. Expression of a variant form of the IFNα/βBP that inhibits IFN activity, but does not interact with cell surface glycosaminoglycans, results in highly attenuated viruses with a virulence similar to that of the IFNα/βBP deletion mutant viruses. Transcriptomics analysis and infection of IFN receptor-deficient mice confirmed that the control of IFN activity is the main function of the IFNα/βBP in vivo. We propose that retention of secreted cytokine receptors at the cell surface may largely enhance their immunomodulatory activity.
URIhttp://hdl.handle.net/10261/178668
DOI10.1038/s41467-018-07772-z
Identifiersdoi: 10.1038/s41467-018-07772-z
issn: 2041-1723
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